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Autophagy: a pathway that contributes to connexin degradation.

ABSTRACT: The function of connexins, which form gap junctions, can be rapidly modulated by degradation, because they have half-lives of only a few hours. Autophagy is a degradation pathway that has been implicated in several diseases and can be induced by cellular stresses such as starvation. We investigated the involvement of autophagy in proteolysis of the wild-type connexins CX50 and CX43, and a cataract-associated connexin mutant, CX50P88S, which forms cytoplasmic accumulations. We observed that cytoplasmic connexins were partially (cup-shaped) or completely (ring-shaped) enclosed by structures containing the autophagy-related protein LC3. Intracellular connexins also colocalized with p62, a protein that might serve as a cargo receptor for autophagic degradation. Starvation induced a decrease in connexin levels that was blocked by treatment with chloroquine, a lysosomal protease inhibitor, or by knockdown of the autophagy-related protein Atg5. These results demonstrate that autophagy can regulate cellular levels of wild-type connexins and imply that the persistence of accumulations of CX50P88S results from insufficient degradation capacity of constitutive autophagy.

SUBMITTER: Lichtenstein A

PROVIDER: S-EPMC3048889 | biostudies-other | 2011 Mar

REPOSITORIES: biostudies-other

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Autophagy: a pathway that contributes to connexin degradation.

Lichtenstein Alexandra A Minogue Peter J PJ Beyer Eric C EC Berthoud Viviana M VM

Journal of cell science 20110301 Pt 6

The function of connexins, which form gap junctions, can be rapidly modulated by degradation, because they have half-lives of only a few hours. Autophagy is a degradation pathway that has been implicated in several diseases and can be induced by cellular stresses such as starvation. We investigated the involvement of autophagy in proteolysis of the wild-type connexins CX50 and CX43, and a cataract-associated connexin mutant, CX50P88S, which forms cytoplasmic accumulations. We observed that cytop ...[more]

PMID: 21378309

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Autophagy: a pathway that contributes to connexin degradation.

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Autophagy: a pathway that contributes to connexin degradation.

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